fibrinopeptide-a and Myocardial-Infarction

Topics: Biomarkers; Blood Coagulation Tests; Cerebral Infarction; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoenzyme Techniques; Myocardial Infarction; Peptide Fragments; Pulmonary Embolism; Radioimmunoassay; Thrombophilia; Venous Thrombosis

Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes (ACS). However, the identification of patients at high-risk for progression of coronary thrombosis is difficult partly because we currently lack clinically meaningful laboratory methods for its detection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflected by plasma or urine concentrations of fibrinopeptide A, is increased in patients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very short half-life of the compound, by artifact due to sample acquisition, and by extremely long turnaround times. To overcome these limitations, measurement of soluble fibrin has been proposed. We have recently explored the prognostic value of a new fibrin-specific ELISA assay for soluble fibrin in patients with ACS and found that patients with the highest levels had a 2-fold increased risk of early and late cardiac events. Increases in plasma concentrations of cross-linked fibrin degradation products (XL-FDPs), which reflect increased fibrin turn-over, are a marker of risk for complications of myocardial infarction. However, until recently, assays for XL-FDPs lacked specificity, because they did not distinguish between fibrin and fibrinogen degradation products. Recently, fibrin-specific ELISAs have been described and a rapid whole blood assay for D-dimer has been developed. We recently validated the prognostic value of this whole blood agglutination assay in patients with ACS. These results suggest that: (1) The detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with biochemical evidence of ongoing coronary thrombosis may particularly benefit from aggressive antithrombotic strategies; (3) sequential measurement of these markers may be useful to guide antithrombotic treatment during the unstable phase of coronary artery disease.

Topics: Angina, Unstable; Coronary Thrombosis; Fibrinopeptide A; Humans; Myocardial Infarction; Prognosis; Prothrombin; Risk Assessment; Sensitivity and Specificity; Time Factors

Topics: Angina Pectoris; Blood Coagulation; Coronary Thrombosis; Fibrinolysis; Fibrinopeptide A; Humans; Myocardial Infarction; Plasminogen Inactivators

Thromboembolic disease continues to plague mankind because it is often detected too late for effective management, because modern therapeutic measures are often inefficiently managed, and because new therapeutic agents and available laboratory tests are ignored. New investigations that continue to be reported in Seminars in Thrombosis and Hemostasis and other journals deserve greater recognition and appreciation. Physicians and other scientists have reached a point at which antithrombotic and hemorrhagic effects of therapeutic anticoagulants can become dissociated if they effectively work together at the many interfaces for research and development among them to harvest the yield of basic research for practical clinical application.

Topics: Antithrombins; Blood Coagulation Tests; Factor X; Factor Xa; Fibrinopeptide A; Heparin; Humans; Intracranial Embolism and Thrombosis; Myocardial Infarction; Oligosaccharides; Prothrombin; Pulmonary Embolism; Thromboembolism

Topics: Angina Pectoris; Blood Coagulation Disorders; Blood Platelet Disorders; Coronary Disease; Coronary Vasospasm; Fibrinopeptide A; Humans; Myocardial Infarction; Prostaglandins; Thromboxanes

Thrombin activity has been implicated as a mechanism for failed reperfusion and reocclusion following thrombolysis. Aggregating platelets provide a phospholipid surface on which prothrombin is cleaved to form thrombin. We examined markers of thrombin generation and activity in patients enrolled in a randomized, placebo-controlled, dose escalating trial of the platelet glycoprotein IIb-IIIa inhibitor eptifibatide (Integrilintrade mark) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction. Measurements were obtained at baseline, at 90 minutes, and at 6, 12, and 24 hours after starting therapy. Eptifibatide inhibited platelet aggregation in response to 20 microM ADP. Levels of fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin fragment 1.2 (F1.2) were not lower in patients treated with eptifibatide than in the control group. In the course of dose escalation, two groups of patients received the same 135 microg/kg bolus of eptifibatide, one with and one without a heparin bolus. FPA levels were dramatically lower in the heparin-treated patients. Levels of FPA, TAT, and F1.2 were not higher in patients with than in those without recurrent ischemia, or in patients without than in those with Thrombolysis in Myocardial Infarction (TIMI) grade 3 angiographic flow at 90 minutes. These data suggest that thrombin generation and activity persist following thrombolysis, despite inhibition of platelet aggregation, and that treatment with inhibitors of thrombin activity may be required even when glycoprotein IIb-IIIa inhibitors are used.

Topics: Cohort Studies; Double-Blind Method; Eptifibatide; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Peptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombin; Thrombolytic Therapy

Angiographic thrombus is associated with increased coronary occlusion and restenosis rates after angioplasty. Administration of intracoronary urokinase decreases the incidence of thrombus but is associated with an increased periprocedural event rate, including stroke and myocardial infarction. An alternative approach is to deliver the agent directly into the arterial wall, thereby reducing the thrombotic substrate in the absence of a systemic effect of the delivered agent.. This randomized, double-blind, prospective study correlated intracardiac fibrinopeptide A levels with the ischemic events after angioplasty and evaluated whether locally administered urokinase could reduce the event rate.. Fifty-four patients with acute coronary syndromes were randomly assigned to local delivery of urokinase or saline. Levels of fibrinopeptide A, a marker of thrombin activity, were obtained before and after administration of heparin, after 2 balloon inflations, and at the end of the procedure in 43 patients and were correlated with ischemic events within the 6-month follow-up period (death, myocardial infarction, or recurrent ischemia).. Multivariant analysis revealed that an elevated fibrinopeptide A level before angioplasty significantly correlated with an increased likelihood of an adverse event over the 6-month clinical follow-up. A postangioplasty reduction in the fibrinopeptide A level was noted in control patients (P <.001), but not after local urokinase administration, and the final fibrinopeptide A level was higher in the urokinase group (P =.02). Urokinase had no effect on the procedural results. On follow-up more patients receiving urokinase (13 of 27) had ischemic events than did control patients (6 of 25, P =.04). Most events were recurrent ischemia caused by restenosis.. Heparin-resistant thrombin activity, as evidenced by an increased fibrinopeptide A level correlates with ischemic events on long-term follow-up. Local delivery of urokinase increased the event rate.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Double-Blind Method; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Pilot Projects; Prospective Studies; Recurrence

We sought to assess the effects of antithrombotic therapy after thrombolysis for acute myocardial infarction on markers of thrombin generation and activity and to determine the relation of these markers with clinical outcomes.. Thrombin activation and generation often occur with thrombolysis for acute myocardial infarction. Antithrombotic regimens have been developed to reduce the resulting thrombotic complications.. We sampled plasma markers of thrombin generation and activity after thrombolysis in 292 patients. We assessed the relations of these markers with clinical outcomes at 30 days.. Fibrinopeptide A (FPA), a marker of thrombin activity toward fibrinogen, was elevated at baseline (12.3 ng/ml) and increased to 18.4 ng/ml by 90 min after streptokinase and subcutaneous heparin treatment. With intravenous heparin, this increase was attenuated, but intravenous heparin did not prevent thrombin generation, as measured by prothrombin fragment 1.2 (F1.2). Heparin level, measured by anti-Xa activity, correlated with activated partial thromboplastin time (aPTT, r = 0.62 to 0.67). Thrombin activity, measured by FPA, was as closely related to aPTT as to the heparin level. Baseline levels of F1.2 were significantly related to the risk of death or reinfarction at 30 days (p = 0.008); values 12 h after enrollment also were related to 30-day mortality (p = 0.05).. Although intravenous heparin partly suppresses the increased thrombin activity associated with thrombolysis, it does not inhibit thrombin generation. The aPTT was as good a measure of suppression of thrombin activity as the heparin level itself. Hematologic markers of thrombin generation were found to be related to the subsequent risk of thrombotic events.

Topics: Aged; Antithrombin III; Confounding Factors, Epidemiologic; Female; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Myocardial Infarction; Peptide Hydrolases; Streptokinase; Thrombin; Thrombolytic Therapy; Thrombosis; Treatment Outcome

To clarify the relationship between the results of intracoronary thrombolytic therapy (ICT) and fibrino-coagulation in patients with acute myocardial infarction (AMI), the thrombin-antithrombin III complex (TAT) and fibrinopeptide A (FPA), as indices of accelerated coagulation, and the plasmin- alpha 2-plasmin inhibitor complex (PIC), as an index of accelerated fibrinolysis in peripheral blood, were measured just before and after heparin injection (5,000 U), and immediately after ICT. Twenty-four patients with AMI were divided into 2 groups according to the results of ICT; successful ICT (group S) and unsuccessful ICT (group F). As a control group (group C), 14 age-matched normal volunteers were also studied. The levels of TAT and FPA before ICT were significantly higher in groups S and F than in group C (p < 0.01). The TAT level before ICT in group F was higher than that in group S (p = 0.07), however, the TAT, FPA and PIC levels showed no significant differences between groups S and F at each sampling time. TAT/PIC before ICT was significantly higher in group F than in group S (F: 0.026 +/- 0.020 vs S: 0.008 +/- 0.004, p < 0.05), whereas there was no remarkable difference in FPA/PIC between groups S and F. These results indicate that hyper-coagulation had occurred in the AMI cases and that coagulation had been more accelerated in group F. TAT/PIC might be an index of the equilibrium of the fibrino-coagulating system. Therefore, TAT/PIC measurement before thrombolytic therapy may be more useful than TAT measurement alone for evaluating recanalization in ICT.

Topics: Aged; alpha-2-Antiplasmin; Antithrombin III; Blood Coagulation; Female; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Hydrolases; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Thrombolytic Therapy

Thrombin activity is increased in the setting of acute myocardial infarction (AMI) and has been shown to increase further after the administration of thrombolytic therapy for acute infarction. This increase in thrombin activity may play an important role in the 15% to 25% rate of failure to achieve initial reperfusion and in the 5% to 15% rate of early reocclusion after initially successful thrombolysis. To investigate potential mechanisms of thrombin formation in vivo, to understand better the balance of coagulation and fibrinolysis during treatment with recombinant tissue-type plasminogen activator (rt-PA), and to investigate the role of hemostatic markers as predictors of clinical events, we measured 3 markers of procoagulant activity: fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TAT), and prothrombin fragment 1.2 (F1.2), and a marker of fibrinogenolytic activity (B beta 1-42) in patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI)-5 study. This trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin as adjunctive antithrombotic therapy with rt-PA administered to patients with AMI. Correlation of markers at 1 hour with clinical outcomes revealed that increased FPA and TAT levels were associated with increased mortality and TIMI grades 0, 1, or 2 flow at 90 minutes; increased F1.2 levels were associated with TIMI grade 0 or 1 flow at 90 minutes; and increased levels of all 3 procoagulant markers were associated with hemorrhagic events. Late (12 to 24 hours) increases in F1.2, TAT, and B beta 1-42 may be predictive of recurrent ischemia. These results suggest that selected markers of procoagulant and fibrinogenolytic activity may be useful in predicting clinical outcomes in patients treated with thrombolytic therapy for AMI.

Topics: Antithrombin III; Biomarkers; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fibrinopeptide A; Hemostasis; Heparin; Hirudin Therapy; Humans; Myocardial Infarction; Peptide Fragments; Peptide Hydrolases; Pilot Projects; Prothrombin; Recombinant Proteins; Thrombolytic Therapy; Treatment Outcome

This prospective study investigated the behavior of thrombin generation and activity during thrombolysis and concomitant heparin administration.. It has been shown that during thrombolytic therapy there is an increase in thrombin generation and activity. Increased thrombin activity is suppressed by concomitant intravenous heparin, but it is unknown whether thrombin generation is also affected.. Thrombin generation was assessed by measuring prothrombin fragment 1 + 2 and thrombin-antithrombin complex plasma levels and thrombin activity by measuring fibrinopeptide A plasma levels. Serial blood samples were obtained before and at 90 min and 24 and 48 h after the administration of streptokinase (15 patients), recombinant tissue-type plasminogen activator (15 patients) or anistreplase (13 patients). An intravenous bolus of heparin (5,000 IU) was administered before the start of thrombolytic therapy, followed by an infusion of 1,000 U/h to maintain an activated partial thromboplastin time > 1.5 times baseline.. During thrombolytic and concomitant heparin therapy, there was an increase in the plasma levels of prothrombin fragment 1 + 2 (baseline 1.08 vs. 2.73 nmol/liter, p < 0.001) and thrombin-antithrombin complex (baseline 6.5 vs. 17.1 micrograms/ml, p < 0.01) at 90 min, whereas no change was observed in fibrinopeptide A at 90 min (baseline 2.8 vs. 3.0 nmol/liter, p = NS).. During thrombolytic therapy with both fibrin-specific and non-fibrin-specific drugs, there is an increase in thrombin generation despite concomitant administration of intravenous heparin.

Topics: Aged; Antithrombin III; Drug Therapy, Combination; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Hydrolases; Prospective Studies; Prothrombin; Recurrence; Thrombin; Thrombolytic Therapy; Time Factors

In 15 patients with acute myocardial infarction who received 1,500,000 U of streptokinase, the gradual appearance of newly synthesized fibrinogen and the fibrinopeptide release during the first 35 h after SK treatment were evaluated. At 5 h the fibrinogen circulating in plasma was observed as the high molecular weight fraction (HMW-Fg). The concentration of HMW-Fg increased continuously, and at 20 h reached values higher than those obtained from normal plasma. HMW-Fg represented about 95% of the total fibrinogen during the first 35 h. The degree of phosphorylation of patient fibrinogen increased from 30% before treatment to 65% during the first 5 h, and then slowly declined to 50% at 35 h. The early rates of fibrinopeptide A (FPA) and phosphorylated fibrinopeptide A (FPAp) release are higher in patient fibrinogen than in isolated normal HMW-Fg and normal fibrinogen after thrombin addition. The early rate of fibrinopeptide B (FPB) release is the same for the three fibrinogen groups. However, the late rate of FPB release is higher in patient fibrinogen than in normal HMW-Fg and normal fibrinogen. Therefore, the newly synthesized fibrinogen clots faster than fibrinogen in the normal steady state. In two of the 15 patients who had occluded coronary arteries after SK treatment the HMW-Fg and FPAp levels increased as compared with the 13 patients who had patent coronary arteries. These results provide some support for the idea that an increased synthesis of fibrinogen in circulation may result in a procoagulant tendency. If this is so, the HMW-Fg and FPAp content may serve as a risk index for thrombosis.

Topics: Adult; Female; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Kinetics; Male; Middle Aged; Myocardial Infarction; Phosphorylation; Streptokinase

Fibrin generation during and after therapy with alteplase may depend on the level of concomitant anticoagulation. The hypothesis that fibrinopeptide A (FPA) levels, as markers of ongoing in vivo fibrin formation, correlate with the angiographic and clinical outcome of thrombolysis is tested.. Serial plasma FPA levels were determined in 334 patients of the randomized European Cooperative Study Group trial comparing heparin versus placebo plus alteplase and aspirin in patients with acute myocardial infarction. Median FPA levels (with the 10th to 90th percentiles) were 21 ng/ml (2-390 ng/ml) before treatment in placebo-allocated patients (n = 166) and increased to 49 (15-580), 34 (4-320), 27 (2-240), 29 (2-430), and 30 (3-390) ng/ml after 0.75, 3, 12, 24, and 36 hours, respectively. In heparin-allocated patients (n = 168), median baseline FPA values were 18 ng/ml (2-210 ng/ml) and decreased to 6 (1-110), 5 (1-75), 5 (1-60), 7 (1-100), and 10 (1-170) ng/ml at corresponding time points (p less than 0.0001 for the difference at each time point). Adequate anticoagulation, defined as no activated partial thromboplastin time value below twice the pretreatment value at 3, 12, 24, and 36 hours after initiation of treatment, was obtained in 48 patients assigned to heparin. It was associated with normal median FPA levels (less than or equal to 4 ng/ml) at all time points compared with 12 (2-80), 16 (2-240), and 15 (2-240) ng/ml at 12, 24, and 36 hours, respectively, in heparin-assigned but inadequately anticoagulated patients (n = 102, p less than 0.001 for each time point). In the heparin-treated group, median FPA values tended to be lower at all time points in patients with patent vessels than in patients with occluded arteries, but the difference was significant only at 24 hours (p = 0.04). FPA levels did not correlate with clinically apparent recurrent ischemia or with left ventricular thrombosis on two-dimensional echocardiography.. During and after thrombolytic therapy with alteplase, the enhanced fibrin generation is suppressed by sustained concomitant anticoagulation with intravenous heparin. Adequate anticoagulation warrants individual titration of the heparin dose. High plasma FPA levels 24 hours after alteplase therapy are specific but insensitive markers of vessel occlusion in anticoagulated patients. They do not correlate with clinical outcome.

Topics: Coronary Vessels; Fibrinopeptide A; Heparin; Humans; Myocardial Infarction; Recurrence; Thrombin; Thrombolytic Therapy; Tissue Plasminogen Activator; Vascular Patency

Fibrinopeptide A (FPA) and beta thromboglobulin (BTG) were measured in 42 patients with acute myocardial infarction (AMI) allocated on admission to one of three groups: 14 patients received a heparin bolus injection of 5000 IU intravenously followed by a 2-hour intravenous infusion (830 IU/hr) (group 1), 14 patients received a heparin bolus of 5000 IU subcutaneously (group 2), and the remaining 14 patients received no anticoagulant treatment (group 3). In group 1 the initially elevated FPA level of 5.8 +/- 1.8 ng/ml dropped to 2.0 +/- 1.5 ng/ml 30 minutes after the intravenous heparin bolus injection of 5000 IU (p less than 0.001) and returned to normal (1.9 +/- 0.8 ng/ml) in 8 of 14 patients. The initially elevated BTG level of 64 +/- 21 ng/ml did not change significantly during intravenous heparin treatment, whereas there was a rapid but only transitory increase in platelet factor 4, (PF4) from 25 +/- 9 to 74 +/- 16 ng/ml (p less than 0.01) after the intravenous heparin bolus. In group 2 the initial FPA of 5.0 +/- 2.3 ng/ml was similarly elevated as in group 1 and dropped to 2.7 +/- 1.7 and 3.3 +/- 1.5 ng/ml 2 and 4 hours after 5000 IU subcutaneously (p less than 0.05), whereas 6 and 8 hours after subcutaneous heparin bolus the mean FPA levels were 4.2 +/- 1.7 and 5.5 +/- 2.0 ng/ml and no more significantly different from the initial FPA values. BTG and PF4 did not change significantly after the subcutaneous heparin bolus. In group 3 the initially elevated mean FPA level of 4.9 +/- 2.4 ng/ml did not change significantly during the first 8 hours after admission, whereas the FPA level 24 hours after admission was 8.4 +/- 3.9 ng/ml and higher than the initial value (p less than 0.01). We conclude that heparin may reduce the elevated FPA level in plasma found in patients with AMI; however, neither subcutaneous nor intravenous heparin in a dosage frequently used is sufficient to consistently normalize the elevated rate of fibrin formation found in these patients.

Topics: Aged; Beta-Globulins; beta-Thromboglobulin; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Infusions, Parenteral; Injections, Subcutaneous; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Platelet Factor 4; Time Factors

In 19 patients with unstable angina pectoris at rest, plasma levels of the platelet-derived proteins beta-thromboglobulin and platelet factor 4 were significantly elevated in blood samples obtained during or within 4 hours after episodes of angina, but were usually normal during quiescent intervals. Plasma levels of the arachidonic acid metabolite thromboxane B2 were less clearly related to angina, and there was no association of angina with levels of the coagulation product fibrinopeptide A. This demonstration of an association of platelet activation and secretion with unstable angina pectoris by radioimmunoassay of circulating platelet constituents offers a new approach to assessment of therapy in ischemic heart disease and suggests that agents that alter platelet function should be evaluated in patients with unstable angina.

Topics: Adult; Aged; Angina Pectoris; beta-Thromboglobulin; Blood Platelets; Electrocardiography; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Factor 4; Thromboembolism; Thromboxane B2

In most cases, sudden cardiac death is triggered by ischemia-related ventricular tachyarrhythmias and accounts for 50% of deaths from cardiovascular disease in developed countries. Chronic elevation of indicators of coagulation activation has been found in patients with coronary heart disease, but a role of coagulation activation as a potential risk factor for ventricular fibrillation (VF) during acute myocardial infarction (MI) has not been investigated.. We enrolled 50 patients with a history of MI, of whom 26 presented with VF in the acute phase of myocardial ischemia; 24 patients had an acute MI without ventricular tachyarrhythmias. Levels of thrombin-antithrombin complexes (TAT), prothrombin fragment F1 + 2 (F1 + 2), fibrinopeptide A (FPA), plasmin-antiplasmin complexes (PAP), protein C, antithrombin, activated partial thromboplastin time (aPTT), thromboplastin time, D-Dimer, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP) were measured in plasma samples of all patients. Blood collection was obtained sequentially in two separate settings. Patients were studied at a median of 351 days after the acute coronary event.. Higher levels of TAT complexes (13.4 +/- 22.2 vs. 3.03 +/- 4.3 microg/l; p = 0.02), FPA (79.7 +/- 132.3 vs. 24.04 +/- 41.3 ng/ml; p = 0.04), and F1+2 (1.89 +/- 1.3 vs. 1.16 +/- 0.5 nmol/l; p = 0.01) were observed in patients with VF compared with patients without ventricular tachyarrhythmias during the acute phase of MI. D-Dimer levels displayed a trend without reaching statistical significance (0.69 +/- 0.48 vs. 0.48 +/- 0.24 mg/l; p = 0.06). No differences were found in hs-CRP (3.25 +/- 4.5 vs. 4.4 +/- 8.8 mg/l; p = 0.5) and fibrinogen (2.8 +/- 0.9 vs. 2.7 +/- 0.9 g/l; p = 0.6) measurements. Repeat assessment of markers of coagulation activation at a median of 847 days revealed a highly significant decrease in patients with VF.. Markers of thrombin generation are transiently increased in patients with VF during the acute phase of MI. These findings have implications for risk assessment and genetic screening of patients prone to VF during acute myocardial ischemia.

Topics: Antithrombin III; Antithrombins; Biomarkers; Cohort Studies; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptide Hydrolases; Protein C; Prothrombin; Thrombin; Thrombin Time; Ventricular Fibrillation

We evaluated assay systems for detection of in vivo thrombin activity in patients with acute myocardial infarction. The study included 31 consecutive patients with acute myocardial infarction treated either with fibrinolytic therapy (FLT), or acute PTCA. Blood samples were drawn at admission, after 30 min, 1 h, 3 h, 6 h, 12 h, 24, and 48 h. Assays related to the enzymatic action of thrombin included fibrinopeptide A ELISA, a novel latex-enhanced photometric immunoassay for soluble fibrin complexes, fibrin monomer antigen, D-dimer antigen, and soluble platelet glycoprotein V, which is released from the platelet surface by thrombin cleavage. The soluble fibrin assay displayed a high degree of correlation with fibrinopeptide A, and no correlation with D-dimer antigen, indicating that this parameter allows monitoring of in vivo thrombin activity in patients with acute myocardial infarction. Fibrin monomer antigen, and D-dimer antigen, were influenced by FLT, indicating cross-reactivity with proteolytic fragments of fibrin. No significant changes in soluble glycoprotein V were observed. The results show that the novel soluble fibrin assay appears to be a promising method for measurement of in vivo fibrin formation in patients with acute myocardial infarction, irrespective of the primary treatment decision for FLT or acute PTCA.

Topics: Angioplasty, Balloon, Coronary; Biomarkers; Cardiovascular Agents; Drug Therapy, Combination; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fibrinopeptide A; Humans; Myocardial Infarction; Platelet Glycoprotein GPIb-IX Complex; Solubility; Thrombin; Time Factors

Tissue factor pathway inhibitor (TFPI) is the endogenous inhibitor of the extrinsic coagulation pathway; however, its involvement during thrombus formation in patients with acute coronary syndromes (ACS) is still unknown.. Transcardiac (aorta/coronary sinus) free and total TFPI (free + lipoprotein-bound form) levels, as well as TFPI/factor Xa (FXa) complex levels, were measured in plasma samples obtained from patients with acute myocardial infarction undergoing primary PTCA and patients with unstable angina undergoing urgent PTCA. Patients with stable angina undergoing elective PTCA served as controls. In addition, prothrombin fragment 1+2 and fibrinopeptide A plasma levels were measured. Samples were collected at baseline, after PTCA, and after stent deployment. In patients with ACS, both total and free TFPI plasma levels in the coronary sinus were significantly lower than the corresponding levels measured in the aorta at any time point of the study; conversely, a significant increase in TFPI/FXa complex plasma levels was observed in the coronary sinus as compared with the aorta. In contrast, in patients with stable angina, no differences were observed in TFPI and TFPI/FXa levels at baseline in the coronary sinus as compared with the aorta.. TFPI is involved in the process of thrombus formation in vivo in patients with ACS, which suggests a potential role for TFPI in modulating coronary thrombosis.

Topics: Aged; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Aorta; Coronary Circulation; Coronary Thrombosis; Coronary Vessels; Factor Xa; Female; Fibrinolysis; Fibrinopeptide A; Heparin; Humans; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prothrombin; Stents; Thrombin; Thrombophilia

Increased levels of markers of hemostasis may assist in the determination of the extent of carotid occlusive disease and the identification of neurologically intact individuals at increased risk of ischemic events.. We conducted a prospective study of 304 subjects, including 82 with a recent (< or =7 days) transient ischemic attack (TIA), 157 asymptomatic individuals with a cervical bruit, and 65 control subjects. Baseline evaluation included a neurological assessment, ECG, cervical ultrasonography, and cerebral CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were also determined. Results were analyzed in relation to the degree of carotid disease and the subsequent occurrence of cerebral and cardiac ischemic events.. Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic events occurred. Survival analyses showed that prothrombin fragment 1.2 (F(1.2)) was a predictor of time to cerebral and cardiac ischemic events in the combined TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81) as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to 2.53). In the TIA group, both F(1.2) (RR, 2.36; 95% CI, 1.19 to 4.68) and severe (> or =80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of time to ischemic stroke, myocardial infarction, or vascular death.. In patients with TIAs and in asymptomatic individuals with cervical bruits, F(1.2) levels were found to be independent predictors of subsequent cerebral and cardiac ischemic events. Our results are consistent with an active role of the coagulation system through upregulation of thrombin in carotid disease progression and in the pathogenesis of ischemic events in patients at risk.

Topics: Aged; alpha-2-Antiplasmin; Antifibrinolytic Agents; Antithrombin III; Biomarkers; Carotid Stenosis; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolysin; Fibrinopeptide A; Hemostasis; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Prognosis; Proportional Hazards Models; Prospective Studies; Prothrombin; Quebec; Risk Factors; Survival Rate

Although thrombus formation plays a major role in acute coronary syndromes, few studies have evaluated a thrombus marker in risk stratification of patients with chest pain. Furthermore, the relation between markers that reflect myocardial injury and thrombus formation that may predict events in a heterogeneous patient population is unknown. This study correlated markers of thrombus and myocardial injury with early and late ischemic events in consecutive patients with chest pain.. Serum troponin I (TnI), myoglobin, and myosin light chain levels were obtained from 247 patients and urinary fibrinopeptide A (FPA) from 178 of the 247. By multivariate analysis, patients with an elevated FPA level were 4.82 times more likely to die or have myocardial infarction, unstable angina, and coronary revascularization at 1 week (P=0.002, 95% CI 1.78, 13.03), whereas those with an elevated TnI (>0.2 ng/mL) were 9.41 times more likely (P<0.001, 95% CI 2.84, 31.17). At 6 months (excluding the index event), an elevated FPA level was an independent predictor of events, with an odds ratio of 9.57 (P<0.001, C1 3.29, 27.8), and was the only marker to predict a shorter event-free survival (P<0.001). The other markers did not independently correlate with cardiac events, although MLC incrementally increased early predictive accuracy in combination with the FPA and TnI.. Elevated FPA and TnI correlated with cardiac events during the initial week in patients presenting to the Emergency Department with chest pain. FPA predicted adverse events and a shorter event-free survival at 6 months.

Topics: Aged; Angina, Unstable; Biomarkers; Chest Pain; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Myoglobin; Myosin Light Chains; Prospective Studies; Sensitivity and Specificity; Time Factors; Troponin I

The purpose of this study was to determine whether the elevated levels of hemostatic markers in the early phase of myocardial infarction may serve as risk factors for subsequent cardiac mortality.. Increased plasma hemostatic markers were noted in acute myocardial infarction, indicating that the blood coagulation system is highly activated in those patients. However, there are few clinical data concerning the association between the elevated hemostatic markers and survival in patients with myocardial infarction.. Blood samples were obtained from 64 patients (mean age 67 +/- 11 years; 49 male) with acute myocardial infarction within 12 h after the onset of symptoms and before the initiation of any antithrombotic treatment. We measured plasma concentrations of fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) using the enzyme-linked immunosorbent assay method, and examined the associations between the level of these markers and survival with Cox proportional hazards models.. The follow-up time was 27 +/- 17 months, and 19 patients died of cardiac causes during the follow-up. Univariate survival analysis identified Killip class IV (hazard ratio 4.86; 95% confidence interval [CI] 1.55-15.19), left ventricular ejection fraction (hazard ratio 0.94; 95% CI 0.90-0.99), FPA (hazard ratio 1.54; 95% CI 1.13-2.10), F1+2 (hazard ratio 2.03; 95% CI 1.17-3.53) and TAT (hazard ratio 1.88; 95% CI 1.27-2.79) as significant factors associated with cardiac mortality. In multivariate analyses, only FPA level (hazard ratio 1.84; 95% CI 1.03-3.30) and left ventricular ejection fraction (hazard ratio 0.93; 95% CI 0.88-0.98) were independent predictors of cardiac mortality.. Elevated FPA in the early phase of myocardial infarction identifies patients with increased risk for subsequent cardiac death. This association appears to be independent of residual left ventricular function after infarction.

Topics: Adult; Aged; Antithrombin III; Biomarkers; Coronary Thrombosis; Female; Fibrinopeptide A; Follow-Up Studies; Hemostasis; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptide Hydrolases; Prognosis; Prothrombin; Risk Assessment; Survival Rate

This study investigates the association between the concentration and function of plasma fibrinogen molecules measured at the time of hospital admission in patients with acute myocardial infarction (AMI), with reference to the risk of new coronary ischemic events during a three-day follow-up period of. Before starting fibrinolytic and anticoagulant treatment plasma fibrinogen, high molecular weight fibrinogen (HMW-fibrinogen), fibrin formation rate (FbFR) and phosphorous content in fibrinogen were determined in 90 AMI patients. During a three-day follow-up period 12 patients suffered new ischemic events. The 12 patients with coronary ischemia had higher concentrations of plasma fibrinogen (312+/-23 vs. 270+/-73 mg/dl, p<0.05) and HMW-fibrinogen (246+/-35 vs. 189+/-23 mg/dl, p<0.001) and a higher FbFR (65+/-30 vs. 40+/-25, p<0.001) than patients without these events. No association was found between the phosphorous content in fibrinogen and new coronary ischemic events. We conclude that after myocardial infarction an elevated plasma level of HMW-fibrinogen and a high FbFR value at the time of hospital admission are associated with new coronary ischemic events during a three-day follow-up period.

Topics: Aged; Biomarkers; Convalescence; Coronary Thrombosis; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Follow-Up Studies; Humans; Male; Middle Aged; Molecular Weight; Myocardial Infarction; Phosphorus; Phosphorylation; Protein Processing, Post-Translational; Recurrence

Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes.. Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA).. FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups.. IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.

Topics: Angina, Unstable; Antithrombin III; Biomarkers; Female; Fibrinopeptide A; Humans; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Prothrombin; Statistics, Nonparametric; Thrombin

The molecular markers of platelet activation, coagulation and fibrinolysis were detected in 60 cases of coronary heart disease (CHD), including 15 cases of stable angina (SA), 21 cases of unstable angina (UA) and 24 cases of acute myocardial infarction (AMI). The results showed that the platelet granule membrane protein 140 (GMP-140) level increased obviously in CHD groups compared with normal control, suggesting that platelet activation existed in CHD. Prothrombin fragment F1 + 2 and fibrinopeptide A (FPA) were examined to observe the activation of coagulation. No difference was found between SA group and normal controls, while their levels in both UA group and AMI group were significantly higher than in normal control and SA group (both P < 0.05). D-D dimer and alpha 2-plasma inhibitor (alpha 2-PI) were detected to observe fibrinolytic state. The results showed that no difference existed between SA group and normal controls, while both D-D dimer and alpha 2-PI in UA group and AMI group were significantly elevated than those in SA group and normal controls (P < 0.05).

Topics: Angina Pectoris; Angina, Unstable; Blood Coagulation; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; P-Selectin; Prothrombin; Thrombophilia

Intravenous heparin, a fundamental therapy in the treatment of patients with acute coronary syndromes, acts by inhibiting thrombin and activated factors X, IX, XI, and XII. It has also been demonstrated that heparin reduces plasma fibrinopeptide A, a marker of thrombin activity, but it is unknown whether it decreases prothrombin fragment 1+2, an indirect marker of thrombin generation. We measured the plasma levels of prothrombin fragment 1+2, fibrinopeptide A, and antithrombin III in 64 consecutive patients with unstable angina or myocardial infarction receiving intravenous heparin. Blood samples were obtained at baseline (before any treatment) and then at 90 minutes and 24 and 48 hours after the administration of an intravenous bolus of heparin (5000 IU) followed by a continuous infusion of 1000 IU per hour to maintain activated partial thromboplastin time at more than double its baseline levels. In comparison with baseline, there was a significant decrease in fibrinopeptide A at 90 minutes and at 24 and 48 hours (baseline, 2.3 nmol/L; 90 minutes, 1.15 nmol/L; 24 hours, 1.4 nmol/L; 48 hours, 1.2 nmol/L; P < .0001) but no change in prothrombin fragment 1+2 levels (baseline, 1.27 nmol/L; 90 minutes, 1.3 nmol/L; 24 hours, 1.33 nmol/L; 48 hours, 1.29 nmol/L; P = NS). Antithrombin III activity decreased at 24 and 48 hours (baseline, 108%; 24 hours, 97%; 48 hours, 95%; P < .0001). Hence, in patients with acute coronary syndromes, intravenous heparin at a dose reaching an activated partial thromboplastin time that adequately suppresses thrombin activity does not suppress increased thrombin generation.

Topics: Acute Disease; Angina, Unstable; Antithrombin III; Biomarkers; Blood Coagulation; Enzyme Activation; Female; Fibrinopeptide A; Heparin; Humans; Injections, Intravenous; Male; Myocardial Infarction; Thrombin; Time Factors

The abrupt cessation of heparin and other thrombin inhibitors when used to treat acute coronary syndromes has been accompanied by a clustering of thrombotic events. It is unknown whether these events are the result of inadequate antithrombin therapy or whether they represent a rebound increase in thrombin activity. This study was designed to determine whether there is a true rebound, as defined by an increase followed by a subsequent decrease, in thrombin activity after discontinuation of intravenous heparin therapy.. Thirty-five patients with recent acute myocardial infarction or unstable angina who had received at least 48 hours of intravenous heparin were studied. Patients underwent ST-segment monitoring, and blood samples for determination of thrombin generation and activity were drawn at 0, 3, 6, 10, and 24 hours after heparin discontinuation. Median aPTT was 65 seconds before heparin discontinuation. Median fibrinopeptide A increased from 9.5 to 16.9 ng/mL at 3 hours (P < .0004) and returned to 10.5 by 24 hours. Prothrombin fragment 1.2 likewise transiently increased, from 0.34 to 0.51 nmol/L at 6 hours (P < .0002). Modified antithrombin III decreased over time (P < .002), and activated protein C increased from 2.3 to 4.5 ng/mL at 3 hours (P < .001). Although there were no clinical thrombotic events in the first 24 hours, 4 patients had evidence of ischemia by ST-segment monitoring at a median of 12 hours after heparin discontinuation. The degree of increase in fibrinopeptide A and prothrombin fragment 1.2 was not found to be associated with baseline diagnosis, duration of heparin therapy, baseline level of antithrombin III, or activated protein C.. This study demonstrates a transient rebound increase in thrombin activity as well as in activated protein C upon abrupt discontinuation of intravenous heparin. Clinicians should be vigilant for associated thrombotic events. Further investigation of the significance, mechanism, and possible prevention of this rebound phenomenon is needed.

Topics: Aged; Angina, Unstable; Blood Coagulation Factors; Blood Coagulation Tests; Coronary Thrombosis; Electrocardiography; Female; Fibrinopeptide A; Heparin; Humans; Infusions, Intravenous; Male; Monitoring, Physiologic; Myocardial Infarction; Myocardial Ischemia; Protein C; Substance Withdrawal Syndrome; Thrombin; Thrombosis

The blood coagulation system is activated in the acute phase of unstable angina and acute myocardial infarction. However, it remains unclear whether augmented function of the hemostatic mechanism serves only as a marker of the acute thrombotic episode or whether a hypercoagulable state persists for a prolonged period after clinical stabilization.. We prospectively measured the plasma concentrations of prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) in consecutive patients presenting with unstable angina (n = 81) or acute myocardial infarction (n = 32), respectively. At 6 months, plasma determinations were repeated in patients experiencing an uneventful clinical course (unstable angina, n = 57; myocardial infarction, n = 23). We quantitated the plasma levels of F1 + 2 and FPA in control patients with stable angina (n = 37) or healthy individuals (n = 32) who were matched for age and sex. The median plasma concentrations of F1 + 2 and FPA are significantly higher in patients presenting with unstable angina (F1 + 2, 1.08 nmol/L; FPA, 2.4 nmol/L) or acute myocardial infarction (F1 + 2, 1.27 nmol/L; FPA, 3.55 nmol/L) compared with patients with stable angina (F1 + 2, 0.74 nmol/L; FPA, 1.3 nmol/L; P < .0001) or healthy individuals (F1 + 2, 0.71 nmol/L; FPA, 0.80 nmol/L; P < .0001). At 6 months, the median plasma levels of F1 + 2 in patients exhibiting an uneventful clinical course did not differ from values obtained at admission (unstable angina, 1.26 versus 1.07 nmol/L, P = NS; myocardial infarction, 1.22 versus 1.29 nmol/L, P = NS), whereas the median plasma levels of FPA in the same two subpopulations were significantly reduced (unstable angina, 1.1 versus 2.9 nmol/L, P = .0003; myocardial infarction, 1.1 versus 3.0 nmol/L; P = .0028).. During the acute phase of unstable angina and myocardial infarction, patients exhibit increased coagulation system activity. Over the next 6 months, patients with unstable angina or myocardial infarction experiencing an uneventful clinical course manifest a persistent hypercoagulable state with minimal generation of fibrin.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Blood Coagulation; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Osmolar Concentration; Peptide Fragments; Prospective Studies; Prothrombin; Reference Values

Topics: Aspirin; Coronary Thrombosis; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Humans; Myocardial Infarction; Thrombin; Tissue Plasminogen Activator

During the acute phase of myocardial infarction, the generation of thrombin is reflected in the sudden rise of fibrinopeptide A (FPA) and the thrombin-antithrombin III (TAT) complex in blood. We have systematically determined the FPA and TAT plasma concentrations over a period of 14 days after acute myocardial infarction in 100 patients. Mean levels of both thrombin markers were the highest on admission, remained elevated over the following few days, and then gradually declined after day 5. Still, by the end of the first week two thirds of the patients had distinctly elevated TAT and FPA levels, and by the end of the second week such an abnormality was present in half of them. Continuous intravenous heparin infusion at a dose of 20,000 units/day, administered for 1 week to patients who had either received (n = 21) or not received (n = 17) streptokinase, led to a significant depression (p less than 0.05) of thrombin markers over the first 48 hours, an effect that did not persist over the subsequent days of treatment. In patients not assigned to heparin treatment, those in heart failure had significantly (p less than 0.05) higher mean TAT and FPA values on days 3, 5, and 7 compared with patients in whom heart failure was absent. Infarct extension, pulmonary embolism, and death were also associated with a rise in one or both thrombin markers, often preceding the onset of clinical symptoms. Thrombinogenesis was not accompanied by changes in mean plasma concentrations of prothrombin, antithrombin III, or alpha 2-macroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antithrombin III; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Hydrolases; Streptokinase; Thrombin

In a majority of instances, both unstable angina and acute myocardial infarction occur secondary to plaque disruption and thrombus formation. Although the pathogenetic substrates are similar the clinical presentations are quite different. It is hypothesized in this editorial review that the amount of acute thrombus formation and specifically fibrin deposition is greater in myocardial infarction than in unstable angina. Both angiographic studies and studies analyzing the response to thrombolytic agents suggest more thrombus in myocardial infarction than in unstable angina. These data have recently been substantiated by angioscopic observations in these acute syndromes suggesting that more platelet-rich (whitish) thrombus occurs in unstable angina and more red thrombus in myocardial infarction. The red thrombus presumably would be more responsive to thrombolytic agents. Furthermore, it is proposed that these differences between syndromes in acute thrombus formation can be explained by the interplay of vessel wall injury, coagulation variables or stasis of blood flow occurring at or after the time of presentation. Therefore, acute myocardial infarction is associated with occlusive, fibrin-rich thrombus, whereas in unstable angina, the thrombus is nonocclusive, mural and possibly more platelet-rich. However, the clinical syndrome that ultimately develops after plaque disruption is dependent not only on the amount of acute thrombus formation but on the net result of all factors that influence the balance between coronary blood supply and myocardial oxygen demand.

Topics: Angina, Unstable; Blood Platelets; Coronary Angiography; Coronary Thrombosis; Endoscopy; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Myocardial Infarction; Plasminogen Inactivators; Thrombolytic Therapy

Plasma levels of fibrinopeptide A (FPA), D-dimer and tissue-plasminogen activator antigen (t-PA-Ag) were measured serially in 38 patients with acute myocardial infarction undergone emergency coronary angiography and/or PTCR (percutaneous transluminal coronary recanalization). A special attention has been focussed in the possible correlation of the variables of coagulation and fibrinolysis with the degree of patency of infarct-related coronary arteries (IRAs). Before PTCR, 26 patients with completely occluded IRAs had significantly higher plasma levels of FPA when compared with those of 12 patients with incompletely occluded IRAs (33.8 +/- 2.4 vs 11.0 +/- 1.3 ng/ml, mean +/- SD, p less than 0.05, respectively). Successful recanalization were resulted in 19 of 26 patients with completely occluded IRAs. Though plasma D-dimer levels significantly increased after PTCR both in patients with or without successful reperfusion, there were neither differences in the two groups before nor after PTCR (154.8 +/- 1.9 to 257.0 +/- 3.0 vs 131.6 +/- 4.8 to 254.9 +/- 4.1 ng/ml, mean +/- SD, respectively). Coronary angiography in 30 patients, performed about a month after the onset of acute myocardial infarction, revealed good patency (the stenosis was less than 90% evaluated according to the American Heart Association Committee Report in 1975) of IRAs in 17 patients and poor patency (the stenosis was 99% or 100%) of IRAs in 13 patients. The former patients had significantly higher plasma levels of t-PA-Ag after 24 hours from the onset than those of the latter patients (26.6 +/- 10.7 vs 17.4 +/- 4.2 ng/ml, mean +/- SD, p less than 0.05, respectively). These findings suggest that the increase in thrombin activity affects unfavorably the patency of IRAs in the evolving of myocardial infarction, and that the responsiveness of endothelial cells to acute phase stimuli such as thrombin and heparin affects favorably the patency of IRAs in the chronic phase; Elevated plasma levels of D-dimer do not necessarily indicate coronary thrombolysis.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Coagulation; Coronary Vessels; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Tissue Plasminogen Activator; Vascular Patency

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta-thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI-1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.

Topics: beta-Thromboglobulin; Female; Fibrinopeptide A; Humans; Male; Myocardial Infarction; Plasminogen Inactivators; Recurrence; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator

Topics: Blood Coagulation; Drug Therapy, Combination; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Myocardial Infarction; Thrombolytic Therapy; Tissue Plasminogen Activator

Topics: Double-Blind Method; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Myocardial Infarction; Prospective Studies; Recombinant Proteins; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator

The mean levels of fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), and soluble fibrin (tPA method) in cancer patients (n = 32) were intermediate between those of patients with cerebral infarction and pancreatitis who had the most abnormal results and patients with myocardial infarction and pneumonia who had the least abnormal results. Patients with disseminated malignancies (n = 16) had significantly higher mean levels of FPA (10.6 vs. 5.3 nmol/l) and TAT (11.0 vs. 4.4 pmol/l) than patients with limited malignancies (n = 16). The difference in soluble fibrin (fibrin monomer, FM; 22.1 vs. 18.0 nmol/l) was not significant. The values of FPA, FM, and TAT in the patient population correlated significantly. There was a negative correlation between the level of antithrombin and test results for FPA (-0.69), FM (-0.48), and TAT (-0.38) in the cancer patients. Even cancer patients with locally limited disease may have elevated FPA, FM, and TAT test results, indicating a state of definite hypercoagulation.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Infarction; Female; Fibrin; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Pancreatitis; Peptide Hydrolases; Pneumonia; Predictive Value of Tests; Reference Values

Acute myocardial infarction was observed in two patients receiving standard intravenous doses of 5-fluorouracil (5-FU)-based chemotherapy. Therefore, the authors prospectively assessed the thrombogenicity of this agent by studying ten patients, six with head and neck cancer and four with gastrointestinal malignancies, receiving 5-FU (1 g/m2/day) as a constant intravenous infusion over a 4-day or 5-day period. The six patients with head and neck cancer also received a single dose of 100 mg/m2 of cisplatin on day 1. Blood samples were obtained preinfusion, 24 hours into the infusion, and postinfusion. Samples were assayed for fibrinopeptide A (FpA) by enzyme-linked immunoassay, for protein C activity (PCa) using a chromogenic substrate (Spectrozyme PCa), and protein C (PCag) and free protein S antigen (PSag) by electroimmunoassay. No patient experienced a thrombotic event. A significant increase was observed in FpA levels during the infusion which returned toward baseline at the conclusion of the infusion. After infusion of 5-FU, the PCa value was significantly lower than the PCag (37 +/- 17 versus 69 +/- 24%; P less than 0.002). No effect on protein S was observed. The changes in the patients receiving 5-FU alone were comparable to those who also received CDDP. The authors conclude that during the infusion of 5-FU, the rise in FpA activation and reduction in PCa as compared to PCag are compatible with activation of coagulation.

Topics: Adult; Aged; Anus Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Fibrinogen; Fibrinopeptide A; Fluorouracil; Humans; Male; Myocardial Infarction; Prospective Studies; Protein C; Tongue Neoplasms

Fibrinopeptide A (FPA) is a very sensitive marker of fibrin generation in vivo. Because an imbalance between thrombogenic and thrombolytic forces may be responsible for the failure to recanalize and for reocclusion of coronary arteries, such a marker could be of eminent value during thrombolytic treatment of acute myocardial infarction. Thirty-four consecutive patients with acute myocardial infarction (peak creatine kinase level, 1,869 +/- 1,543 IU/l) were treated with 100 mg recombinant tissue-type plasminogen activator (rt-PA) 3.1 +/- 1.1 hours after onset of chest pain. Angiography 12.5 +/- 6.1 days later revealed an 81% patency rate of the infarct-related vessel. FPA plasma levels (normal, 1.9 +/- 0.5 ng/ml) were 34 +/- 46 ng/ml on admission and 93 +/- 86 ng/ml (538 +/- 674% with respect to each patient's admission level) after 90 minutes of rt-PA infusion (p less than 0.01). In patients without evidence of reocclusion (including three primary failures), FPA levels fell under continuous heparin infusion to 6.7 +/- 9.7 ng/ml (24 +/- 33%, p less than 0.01) within 30 minutes and were 3.1 +/- 2.2 ng/ml (15 +/- 15%, p less than 0.01), 1.6 +/- 1.1 ng/ml (8 +/- 10%, p less than 0.01), and 2.5 +/- 3.0 ng/ml (12 +/- 16%, p less than 0.01) 30 minutes, 9 hours, and 21 hours, respectively, after completion of rt-PA therapy. Five patients sustained intermittent or permanent coronary reocclusion after primary thrombolytic success. Their early postlytic FPA levels (13-51 ng/ml) remained high or increased again despite adequate anticoagulation. FPA allows the monitoring of fibrin generation during acute myocardial infarction and thrombolytic therapy. Despite successful recanalization, fibrin generation is increased under rt-PA administration before anticoagulation. Patients under anticoagulation with postlytic FPA levels less than 5 ng/ml or below their admission value seem to be at low risk of reocclusion for several days. FPA levels that are persistently high or that increase again despite adequate anticoagulation indicate ongoing fibrin generation. However, whether FPA can indeed be considered a useful marker of reocclusion remains to be confirmed in a larger population of patients with acute myocardial infarction.

Topics: Coronary Angiography; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Radioimmunoassay; Recombinant Proteins; Recurrence; Time Factors; Tissue Plasminogen Activator

Coronary spasm is the mechanism most often postulated to explain the rare combination of myocardial infarction and angiographically normal coronary arteries, although the reported evidence for its role is circumstantial rather than conclusive. Whereas the importance of thrombosis in myocardial infarction is uncontested in the presence of significant coronary artery disease, there is little in vivo evidence for thrombosis in angiographically normal coronary arteries. Among 11 consecutive patients with acute myocardial infarction undergoing thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) 3.2 +/- 0.7 h after onset of chest pain, and angiography 10.2 +/- 4.5 days later, three young men had normal coronary arteries. Their cases are documented electrocardiographically, enzymatically and angiographically. Mean plasma levels of fibrinopeptide A (FPA) and beta-thromboglobulin (BTG) were clearly elevated before and during rtPA therapy: FPA 52 +/- 41 ng ml-1, BTG 257 +/- 46 ng ml-1. They did not differ significantly from corresponding mean plasma levels in the eight patients with severe coronary artery disease: FPA 67 +/- 66 ng ml-1, BTG181 +/- 75 ng ml-1. We conclude that fibrin formation and platelet activation are probably equally important in the early hours of myocardial infarction, whether or not significant coronary artery disease is present.

Topics: Adult; Angiography; Arteries; beta-Thromboglobulin; Blood Platelets; Coronary Vasospasm; Coronary Vessels; Fibrin; Fibrinopeptide A; Humans; Male; Myocardial Infarction; Platelet Factor 4; Tissue Plasminogen Activator

Fibrinopeptide A (FPA) levels were determined in 40 consecutive patients admitted to the coronary care unit with a typical history of chest pain: in 24 of them a diagnosis of acute myocardial infarction (AMI) and in 16 a diagnosis of angina was made. Seven of the patients with AMI suffered from recurrent episodes of early post-infarctional angina. FPA levels were determined in each patient on admission and every 4 h for 48 h. On admission in patients with both angina and AMI the FPA levels were significantly higher than in normal controls; these levels were higher in patients with AMI than in those with angina, but this difference was not significant. In patients with angina the values decreased progressively after 12 h to baseline values, while in those with AMI the high levels of FPA persisted throughout the 48-hour observation period. In many instances, particularly after 24 h, the differences between the two groups were statistically significant. In patients with early post-infarctional angina the episode of angor was preceded by or corresponded to a new great elevation of FPA levels. These data suggest that the thrombin generation is higher and more prolonged in patients with AMI than in those with angina; the determination of FPA levels, which are an index of 'in vivo' thrombin generation, can be useful to follow the clinical course of ischaemic heart disease.

Topics: Adult; Aged; Angina Pectoris; Coronary Disease; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Myocardial Infarction

Topics: Aged; Blood Coagulation; Cerebral Infarction; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Middle Aged; Myocardial Infarction; Neoplasms; Peptide Fragments

Because acute coronary thrombosis can cause unstable coronary artery disease, fibrinopeptide A, a reliable marker of coagulation activity, may play a role in the evaluation of unstable ischemic syndromes. A new method of fibrinopeptide A sampling, spot urine normalized to urinary creatinine, was evaluated in patients with stable and unstable angina pectoris and acute myocardial infarction. Serial samples were obtained to characterize the changes in urinary fibrinopeptide A levels over time in patients with ischemic heart disease. Admission values (mean +/- SD) were similar in the control group (3.3 +/- 1.4 ng/mg creatinine) and the stable angina group (3.2 +/- 1.1 ng/mg creatinine) (p = NS). Values in the unstable angina group (5.7 +/- 2.6 ng/mg creatinine) were higher than those in the control (p = 0.008) and stable angina (p less than 0.001) groups. Myocardial infarction admission values (8.4 +/- 10.0 ng/mg creatinine) were higher than those in the control (p = 0.005) and stable angina (p less than 0.001) groups, but not higher than those in the unstable angina group. Peak values (the highest of multiple samples) were higher in the unstable angina group (7.6 +/- 5.9 ng/mg creatinine) than in the stable angina group (4.0 +/- 1.0 ng/mg creatinine) (p = 0.04), but not in the control group (4.5 +/- 1.9 ng/mg creatinine) (p = 0.056). The two patients with unstable angina with the highest peak values subsequently exhibited infarction. Peak values in patients with infarction (44.5 +/- 60.0 ng/mg creatinine) were significantly higher than those in patients with unstable (p = 0.03) or stable (p = 0.002) angina and control patients (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angina Pectoris; Angina, Unstable; Coronary Disease; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies

In order to define some of the determinants of successful thrombolysis and reocclusion during fibrinolytic therapy for acute myocardial infarction (AMI), specific molecular markers of fibrin metabolism were serially measured in 15 patients with AMI treated with tissue-type plasminogen activator (t-PA). Fibrin formation was assessed by measurement of fibrinopeptide A (FpA) and fibrinolysis by assay of B-beta peptides 1-42 and 15-42 and crosslinked fibrin degradation products (XDP). At baseline, FpA levels were high while markers of fibrinolysis were near normal. Following a 90-minute infusion of t-PA (0.5-1.1 mg kg-1 hr-1), all markers of fibrinolysis increased. Levels of FpA remained elevated despite heparin at the initiation of cardiac catheterization. None of these markers discriminated between patients with successful reperfusion from those without. At 4 hours, B-beta 15-42 peptide and XDP levels remained elevated suggesting persistence of fibrinolysis beyond the short circulatory half-life of t-PA. FpA levels at 4 hours were lower in patients who underwent acute coronary angioplasty compared to those who received additional low dose t-PA (12.3 +/- 4.5 vs. 30.4 +/- 5.5 ng/ml, p less than 0.05). By 48 hours, markers of fibrinolysis had returned toward normal except in 2 patients with persistently elevated B-beta 15-42 peptide levels who suffered reocclusion on days 5 and 6 (75 and 44 vs. 29 +/- 3 nM, p less than 0.005). In conclusion, molecular markers of fibrin metabolism during fibrinolytic therapy may provide clinically relevant data.

Topics: Angioplasty, Balloon; Catheterization; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Reproducibility of Results; Thrombin; Time Factors; Tissue Plasminogen Activator

In order to determine the role of thrombosis in the acute coronary syndromes the blood levels of fibrinopeptide A and protein C were examined with an enzyme-immune test in 48 patients treated in the cardiological clinic of the National Centre for Cardiovascular Diseases. 27 patients were with transmural myocardial infarction and 21 patients were with non-transmural myocardial infarction. The average time of the test from the onset of pain is 18.4 +/- 12.2 hours (from 3 up to 72 hours). The mean level for fibrinopeptide A for the whole group of patients is 4.95 +/- 3.1 ng/ml and that of protein C is 70.1 +/- 9.8%. For the group of patients with transmural myocardial infarction the level of fibrinopeptide A is 6.09 +/- 3.49 ng/ml and of protein C is 65.3 +/- 8.0%. For the patients with nontransmural myocardial infarction the levels are respectively 3.49 +/- 1.7 ng/ml for fibrinopeptide A and 76.3 +/- 8.3% for protein C. The difference between the two groups is statistically significant (p less than 0.005). In the patients with non-transmural myocardial infarction from whom the blood for the test was taken before the 24th hour the fibrinopeptide A level is 4.8 +/- 2.4 ng/ml and the protein C level is 69.0 +/- 7.8%. The deviations from the reference group are statistically significant (p less than 0.04). The practical importance of these results is discussed.

Topics: Acute Disease; Aged; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Protein C

Topics: Creatine Kinase; Fibrinogen; Fibrinopeptide A; Humans; Injections, Intravenous; Myocardial Infarction; Streptokinase

To assess whether the intense thrombotic state known to occur early after the onset of acute myocardial infarction is further exacerbated by impaired intrinsic fibrinolysis, we compared the intensity of fibrinolysis as measured by the level of crosslinked fibrin degradation products (XL-FDP) in plasma with the intensity of thrombosis as assessed by fibrinopeptide A (FPA) in 98 patients with transmural and 14 patients with non-Q wave infarction. Patients without complications of infarction such as shock, mural thrombi, or malignant arrhythmias requiring countershock generally had normal plasma levels of XL-FDP, less than or equal to 300 ng/ml (81% of those presenting less than 8 hours after onset and 66% of those presenting greater than 8 hours after onset) on admission despite elevated FPA indicative of ongoing thrombosis. In contrast, patients with complications generally had elevated levels of XL-FDP greater than 300 ng/ml (80% of those presenting early and 62.5% of those presenting late) and 50% of these patients had marked elevations to greater than 1000 ng/ml. FPA was markedly elevated in patients with complications whether they presented early or late after onset of infarction. Our direct measurements at the time of infarction support previous data indicating that intrinsic fibrinolysis is impaired in patients with acute infarction, despite marked thrombin activity, when complications are not present. However, when complications are present initially, a more exuberant fibrinolytic response is observed perhaps due to thrombosis associated with the complications themselves.

Topics: Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Time Factors

Increased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ml). and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. However, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Topics: Collagen Diseases; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Liver Cirrhosis; Myocardial Infarction; Neoplasms; Thromboembolism

Fibrinopeptide A (FpA) concentrations in plasma and in 24 hr urine specimens as well as beta-thromboglobulin (BTG) in plasma were measured in 17 patients with severe angina pectoris, including both stable and unstable angina, and in 19 patients with acute myocardial infarction. Patients with unstable angina had plasma FpA and BTG levels of 5.2 +/- 1.7 ng/ml and 91 +/- 23 ng/ml, respectively. The corresponding concentrations of FpA in the 24 hr urine specimens were 8.2 +/- 1.4 micrograms/24 hr. These values were similar to those measured in patients with acute myocardial infarction and higher than the corresponding levels in patients with stable angina (p less than .05) and in normal control subjects (p less than .01). The similarity of the platelet and coagulation findings in patients with unstable angina and in those with myocardial infarction favors the hypothesis that coronary thrombosis may play a major role in the pathogenesis of acute myocardial infarction.

Topics: Angina Pectoris; Beta-Globulins; beta-Thromboglobulin; Blood Coagulation; Fibrinogen; Fibrinopeptide A; Humans; Myocardial Infarction

Fifty patients suffering from acute myocardial infarction were evaluated for beta-thromboglobulin and fibrinopeptide A (FpA) during the first 12 hours after admission. It has been noted that beta-thromboglobulin levels were higher than normal in most of patients examined, whereas FpA levels were higher only in four cases. On the contrary, after 12 hours beta-thromboglobulin levels were normal in all subjects whereas FpA levels showed the same high values. These results indicate that platelets may play an important role only in the acute phase of infarction and that the thrombus formation, accounted for by presence of fibrinogen derivative, only later might occur.

Topics: Beta-Globulins; beta-Thromboglobulin; False Negative Reactions; False Positive Reactions; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Myocardial Infarction; Time Factors

To determine whether coronary thrombosis in vivo is reflected by elevations in levels of fibrinopeptide A (FPA) in plasma, we sequentially characterized plasma FPA levels associated with evolving infarction in patients admitted to the cardiac care unit early after the onset of symptoms, in patients with transmural infarction admitted later, and in patients with nontransmural infarction. Studies were also performed in patients in whom the diagnosis of infarction was suspected but subsequently excluded. FPA values were significantly higher in patients with transmural infarction (42.3 +/- 11.2 ng/ml [mean +/- SEM], n = 53) compared with those in patients with nontransmural infarction (4.8 +/- 1.6 ng/ml, n = 17) or with those in patients in whom infarction was subsequently excluded as a diagnosis (3.5 +/- 0.6 ng/ml, n = 17, p less than .01 for both). Elevations in FPA level were greatest in patients with transmural infarction from whom samples were obtained soon after the onset of symptoms. Thus, in 39 patients from samples were obtained within 10 hr after the onset of symptoms, FPA levels were significantly higher than in 14 patients from whom samples were obtained initially more than 10 hr after the onset of symptoms (55.5 +/- 14.7 vs 4.9 +/- 1.4 ng/ml, p less than .01). In 30 of the 39 patients with evolving transmural infarction from whom samples were obtained within the first 10 hr after the onset of symptoms, the level of FPA was greater than 8 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Coronary Disease; Creatine Kinase; Female; Fibrinogen; Fibrinopeptide A; Humans; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Time Factors

Urinary fpA excretion and fpA in plasma were studied in patients with peripheral artery disease, aortic aneurysm, severe coronary artery disease, acute myocardial infarction and in normal controls. Mean urinary fpA was significantly higher in all groups of patients than in normal controls whose excretion was 1.9 +/- 1.2 micrograms/24 hours (mean +/- SD). We found a good correlation between urinary fpA excretion and plasma fpA (r = 0.68, p less than 0.01, n = 81). The highest levels of urinary fpA were found in 9 patients with aortic aneurysm (11.9 +/- 6.1 micrograms/24 hours). The 10 patients with acute myocardial infarction had also abnormally elevated values (4.3 +/- 1.8 micrograms/24 hours) which were only slightly higher than the levels found in another 10 patients with myocardial infarction receiving subcutaneous heparin in a dosage of 2 X 5000 IU daily (2.9 +/- 1.7 micrograms/24 hours). The 13 patients with peripheral artery disease showed an increase in urinary fpA excretion from 4.0 +/- 1.7 to 10.5 +/- 2.3 micrograms/24 hours after percutaneous angioplasty (p less than 0.001). These data demonstrate that urinary fpA excretion may represent a valid means to detect the cumulative effect of thrombin action on fibrinogen in patients with atherosclerotic vascular disease and after therapeutic intervention.

Topics: Aortic Aneurysm; Arteriosclerosis; Fibrinogen; Fibrinopeptide A; Humans; Myocardial Infarction; Radioimmunoassay

The purpose of this study was to investigate the degree of platelet activation and thrombin generation in 40 patients with stable angina pectoris and in 20 patients with acute myocardial infarction (AMI) by determining the plasma beta thromboglobulin (BTG) and fibrinopeptide A (FPA) concentrations. In patients with angina pectoris increased platelet activation correlated with extensive coronary pathology; the activation, however, was not influenced by a previous myocardial infarction, use of oral anticoagulants, beta-blocking agents, or hyperlipidemia. The plasma beta thromboglobulin concentration predicted more accurately the extent of the coronary artery disease than the functional angina pectoris classification. Thrombin generation was within the normal range. In patients with acute myocardial infarction increased platelet activation and enhanced thrombin generation were found, which were not related to the infarct localization, infarct size, or the presence of complications. Consequently, in these patients determination of plasma beta thromboglobulin and fibrinopeptide A concentrations is useless for the diagnosis of venous thromboembolism.

Topics: Adult; Aged; Angina Pectoris; Beta-Globulins; beta-Thromboglobulin; Blood Platelets; Coronary Disease; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Myocardial Infarction; Myocardium; Thrombin; Thrombophlebitis

The plasma level of fibrinopeptide A (fpA) was used as an index of thrombin action on fibrinogen in order to investigate the rates of fibrin formation and the effect of heparin on thrombin in patients with acute myocardial infarction. The fpA levels measured on admission in 19 patients with acute myocardial infarction ranged from 1.7 to 12.4 ng/ml and were elevated (greater than 2.5 ng/ml) in 16 patients. A loading dose of 5000 IU of heparin resulted in a significant decrease within 20 min of the mean fpA level (from 5.1 to 2.2 ng/ml; p less than .001) and in an fpA normalization in five of 16 patients. During the following continuous infusion of 20,000 IU of heparin per day, the mean fpA levels measured on day 0, 1, and 2 were 3.0, 3.2, and 3.4 ng/ml, respectively, with 16 of 46 fpA values within the normal range. In 10 additional patients, the effect of higher concentrations of heparin and the consequences of stopping heparin infusion were studied. An additional 5000 IU of heparin injected intravenously during continuous infusion of 20,000 IU of heparin per day resulted in a substantial decrease of the plasma fpA level in three of 10 measurements. The stopping of heparin infusion led to an impressive increase of the mean fpA level (from 3.1 to 12.9 ng/ml; p less than .001) within 2 hr. These data demonstrate increased fibrin formation in patients with acute myocardial infarction and neutralization of thrombin in vivo by heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Antithrombin III; Creatine Kinase; Female; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Infusions, Parenteral; Male; Middle Aged; Myocardial Infarction

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet release and thrombin generation respectively, were measured in 48 patients within 3 days of admission to hospital for acute chest pain. Twenty-one patients had a confirmed myocardial infarction (MI); 15 had unstable angina without infarction; and 12 had chest pain due to noncardiac causes. FPA and BTG were also measured in 23 control hospital patients of similar age. Mean plasma BTG levels were not significantly different in the 4 groups. Mean plasma FPA levels were significantly higher in all 3 groups with acute chest pain when compared to the control subjects (p less than 0.01), but there were no significant differences between the 3 groups. Increased FPA levels in patients with acute chest pain are not specific for myocardial infarction, nor for ischaemic chest pain.

Topics: Adult; Aged; Angina, Unstable; Beta-Globulins; beta-Thromboglobulin; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Pain; Thorax

The effect of discontinuation of a long term oral anticoagulant therapy with phenprocoumon on blood clotting parameters has been evaluated in patients in a controlled prospective trial. After termination of phenprocoumon the prothrombin time normalized within 15 days and the thrombotest coagulation value within 57 days. Fibrinopeptide A (FPA) increased significantly during the observation period. FPA release in vitro also rose after discontinuation of anticoagulants. In control patients on a phenprocoumon maintenance therapy no alterations of the above mentioned parameters occurred within the same period. The data indicate that plasma hypercoagulability is found in many patients, orally anticoagulated because of myocardial infarction, when the anticoagulant therapy is discontinued.

Topics: 4-Hydroxycoumarins; Administration, Oral; Aged; Anticoagulants; Blood Coagulation; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Myocardial Infarction; Phenprocoumon; Prothrombin Time; Thromboembolism; Time Factors

In vivo platelet alpha-granule release and fibrin I formation were measured in 82 patients with ischemic heart disease by radioimmunoassay of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A. The presence and extent of coronary artery disease were determined by coronary arteriography, and the extent of left ventricular regional dysfunction was assessed by contrast left ventriculography. In patients with abnormal coronary arteriograms without previous myocardial infarction, mean levels of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were not elevated. In patients in whom myocardial infarction had occurred more than 6 mo previously, platelet factor 4 (8.3 ng/ml; p less than 0.01) and beta-thromboglobulin (33.2 ng/ml; p less than 0.001) levels were significantly elevated, but fibrinopeptide A levels were normal. Levels of platelet factor 4 and beta-thromboglobulin were unrelated to the extent of coronary artery disease. In the patients with prior infarction, beta-thromboglobulin correlated directly with extent of left ventricular regional dysfunction (r = 0.53; p less than 0.01) and inversely with ejection fraction (r = -056; p less than 0.05). In a small group of patients with left ventricular aneurysm, mean fibrinopeptide A levels were also elevated. We interpret these findings as indicating that platelet release in patients with ischemic heart disease results from platelet reaction with previously infarcted myocardium rather than with the atherosclerotic coronary arteries.

Topics: Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Blood Coagulation Factors; Blood Platelets; Coronary Angiography; Coronary Disease; Female; Fibrinogen; Fibrinopeptide A; Heart Aneurysm; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Factor 4

Topics: Adolescent; Adult; Aged; Animals; Brain Abscess; Burns; Child; Circadian Rhythm; Dogs; False Positive Reactions; Female; Fibrinogen; Fibrinopeptide A; Hemoglobinuria; Humans; Hydrogen-Ion Concentration; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Myocardial Infarction; Neoplasms; Thrombin

Topics: Acute Disease; Fibrinogen; Fibrinopeptide A; Humans; Myocardial Infarction

Fibrinopeptide A (FPA), which is considered to be a quantitative indicator for the thrombin activity in vivo, was measured in 136 patients treated with phenprocoumon in order to obtain information on the effectiveness of the inhibition of the coagulation system. The results show a decrease of the FPA concentration in relation to the efficacy of the anticoagulant therapy as measured by the thrombotest coagulation method (p less than 0.01). However, elevated FPA was observed even under an effective oral anticoagulation. These data indicate that an increased thrombin activity cannot be completely prevented by oral anticoagulants in every patient. Combined measurement of FPA and the thrombotest coagulation methods might be used to detect patients with an elevated risk of recurrent thromboembolism despite treatment with phenprocoumon.

Topics: 4-Hydroxycoumarins; Administration, Oral; Anticoagulants; Blood Coagulation; Fibrinogen; Fibrinopeptide A; Humans; Myocardial Infarction; Partial Thromboplastin Time; Phenprocoumon; Thrombin; Thrombophlebitis

Topics: Acute Disease; Blood Coagulation; Electrocardiography; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Count; Time Factors